The invention relates to monoclonal antibodies.
It concerns monoclonal antibodies to terbinafine (Lamisil®), i.e. to (E)-N-(6,6-dimethylhept-2-en-4-ynyl)-N-methyl-1-naphthalene methanamine of formula I
in free form or salt form, particularly hydrochloride salt form,hereinafter briefly named “the antibodies of the invention”.
Terbinafine is an antimycotic agent marketed worldwide in both oral and topical formulations, particularly for the treatment of fungal infections of the skin, nail and hair. It is a representative of the allylamine class of synthetic antifungal agents, which is chemically and mechanistically distinct from the other antimycotic drugs used clinically.
One of the advantages of terbinafine resides in its very low immunogenicity. Thus, although it has been on the market for several years, so far no reports have appeared in the literature describing strong immune responses thereto. While this is of clinical benefit, it renders detection of the drug by immunological methods problematic, even when it is coupled to immunogenic protein to enhance immune response.
Further, in view of its widespread use, development of a simple immunoassay procedure allowing easy and speedy detection of terbinafine in body fluids, tissues or compartments of a patient, e.g. serum or nails, would be very desirable. Monitoring e.g. blood or nail levels of terbinafine in patients with particular reference to treatment failure (dermatophytoma) is very desirable for fine tuning of the dosage administered and better understanding of the mode of action so as to maintain the minimum level sufficient for beneficial pharmacological activity in, e.g., onychomycosis. However, there have been no previous reports of monoclonal antibodies which recognize terbinafine, possibly due to inherent difficulties in making such antibodies in view of the low immunogenicity of the drug mentioned above.